Cargando…

Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors—plexin Bs. Recently, Sema4D has be...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Junhua, Wu, Shouzhen, Cao, Sancheng, Zhu, Xieying, Zhang, Shuwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759398/
https://www.ncbi.nlm.nih.gov/pubmed/33381571
http://dx.doi.org/10.1155/2020/6663291
_version_ 1783627103230492672
author Huang, Junhua
Wu, Shouzhen
Cao, Sancheng
Zhu, Xieying
Zhang, Shuwan
author_facet Huang, Junhua
Wu, Shouzhen
Cao, Sancheng
Zhu, Xieying
Zhang, Shuwan
author_sort Huang, Junhua
collection PubMed
description Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors—plexin Bs. Recently, Sema4D has been reported to exert a proinflammatory effect on the endothelium and to be involved in cardiovascular disease. However, the role of Sema4D in KD remains unknown. This study was aimed at revealing the change of soluble Sema4D (sSema4D) in the serum of patients with KD and the effect of the sSema4D-plexin axis on the production of proinflammatory cytokines from human coronary endothelial cells (HCAECs) stimulated with sera from KD patients. Our results showed that serum sSema4D levels were specifically elevated in KD patients, especially in those with CALs, and correlated positively with disease severity and serum concentrations of interleukin- (IL-) 1β, IL-6, and IL-8. The disintegrin and metalloproteinase domain 17- (AMAM17-) mediated Sema4D shedding from neutrophils contributed to the elevation of sSema4D in the serum of KD patients. Furthermore, we found that Sema4D induced IL-1β production of HCAECs via plexin B2, whereas it promoted IL-6 and IL-8 production via plexin B1. Moreover, the expression of both plexin B1 and plexin B2 was upregulated in HCAECs treated with KD sera, and silencing of the two plexin receptors suppressed the overexpression of IL-1β, IL-6, and IL-8 in KD serum-treated HCAECs. Thus, our findings indicated that sSema4D released from neutrophils participates in the pathogenesis of KD-CALs by promoting inflammatory cytokine production of ECs via both plexin B1 and plexin B2, and Sema4D may be a novel predictor for KD-CALs and a candidate therapeutic target for anti-inflammatory strategies of KD.
format Online
Article
Text
id pubmed-7759398
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-77593982020-12-29 Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease Huang, Junhua Wu, Shouzhen Cao, Sancheng Zhu, Xieying Zhang, Shuwan Biomed Res Int Research Article Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors—plexin Bs. Recently, Sema4D has been reported to exert a proinflammatory effect on the endothelium and to be involved in cardiovascular disease. However, the role of Sema4D in KD remains unknown. This study was aimed at revealing the change of soluble Sema4D (sSema4D) in the serum of patients with KD and the effect of the sSema4D-plexin axis on the production of proinflammatory cytokines from human coronary endothelial cells (HCAECs) stimulated with sera from KD patients. Our results showed that serum sSema4D levels were specifically elevated in KD patients, especially in those with CALs, and correlated positively with disease severity and serum concentrations of interleukin- (IL-) 1β, IL-6, and IL-8. The disintegrin and metalloproteinase domain 17- (AMAM17-) mediated Sema4D shedding from neutrophils contributed to the elevation of sSema4D in the serum of KD patients. Furthermore, we found that Sema4D induced IL-1β production of HCAECs via plexin B2, whereas it promoted IL-6 and IL-8 production via plexin B1. Moreover, the expression of both plexin B1 and plexin B2 was upregulated in HCAECs treated with KD sera, and silencing of the two plexin receptors suppressed the overexpression of IL-1β, IL-6, and IL-8 in KD serum-treated HCAECs. Thus, our findings indicated that sSema4D released from neutrophils participates in the pathogenesis of KD-CALs by promoting inflammatory cytokine production of ECs via both plexin B1 and plexin B2, and Sema4D may be a novel predictor for KD-CALs and a candidate therapeutic target for anti-inflammatory strategies of KD. Hindawi 2020-12-16 /pmc/articles/PMC7759398/ /pubmed/33381571 http://dx.doi.org/10.1155/2020/6663291 Text en Copyright © 2020 Junhua Huang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Junhua
Wu, Shouzhen
Cao, Sancheng
Zhu, Xieying
Zhang, Shuwan
Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title_full Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title_fullStr Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title_full_unstemmed Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title_short Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease
title_sort neutrophil-derived semaphorin 4d induces inflammatory cytokine production of endothelial cells via different plexin receptors in kawasaki disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759398/
https://www.ncbi.nlm.nih.gov/pubmed/33381571
http://dx.doi.org/10.1155/2020/6663291
work_keys_str_mv AT huangjunhua neutrophilderivedsemaphorin4dinducesinflammatorycytokineproductionofendothelialcellsviadifferentplexinreceptorsinkawasakidisease
AT wushouzhen neutrophilderivedsemaphorin4dinducesinflammatorycytokineproductionofendothelialcellsviadifferentplexinreceptorsinkawasakidisease
AT caosancheng neutrophilderivedsemaphorin4dinducesinflammatorycytokineproductionofendothelialcellsviadifferentplexinreceptorsinkawasakidisease
AT zhuxieying neutrophilderivedsemaphorin4dinducesinflammatorycytokineproductionofendothelialcellsviadifferentplexinreceptorsinkawasakidisease
AT zhangshuwan neutrophilderivedsemaphorin4dinducesinflammatorycytokineproductionofendothelialcellsviadifferentplexinreceptorsinkawasakidisease